HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA.
HuR and TIA1/TIAL1 are involved in regulation of alternative splicing of SIRT1 pre-mRNA.
复制标题
HuR 和 TIA1/TIAL1 参与 SIRT1 前 mRNA 选择性剪接的调节。
DOI：
10.3390/ijms15022946
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发表时间：
2014-02-20
影响因子：
5.6
通讯作者：
Guo D
中科院分区：
文献类型：
--
作者：
Zhao W;Zhao J;Hou M;Wang Y;Zhang Y;Zhao X;Zhang C;Guo D
SIRT1是一种多效蛋白，在代谢、衰老、长寿、应激反应和癌症中发挥着重要的多功能作用，已成为一系列疾病的重要治疗靶点。最近的研究表明，SIRT1前mrna经历选择性剪接以产生不同的同种异构体，如SIRT1全长和SIRT1-ΔExon8变体。先前的研究表明，这些SIRT1 mRNA剪接变体向该蛋白传递了不同的特征和功能，这可能反过来解释了SIRT1的多功能作用。然而，SIRT1选择性剪接调控的机制仍有待阐明。我们的目标是寻找调节SIRT1选择性剪接的新途径。在这里，我们描述的实验表明，在正常和应激情况下，两种rna结合蛋白HuR和TIA1/TIAL1参与SIRT1前mRNA选择性剪接的调节：HuR通过促进SIRT1外显子8的排除而增加SIRT1-ΔExon8，而TIA1/TIAL1抑制外显子8的排除导致SIRT1-ΔExon8 mRNA水平的降低。这项研究为SIRT1前mrna的选择性剪接如何被调控提供了新的见解，这对理解SIRT1的关键和多功能作用具有重要意义。
SIRT1 is a pleiotropic protein that plays critical and multifunctional roles in metabolism, senescence, longevity, stress-responses, and cancer, and has become an important therapeutic target across a range of diseases. Recent research demonstrated that SIRT1 pre-mRNA undergoes alternative splicing to produce different isoforms, such as SIRT1 full-length and SIRT1-ΔExon8 variants. Previous studies revealed these SIRT1 mRNA splice variants convey different characteristics and functions to the protein, which may in turn explain the multifunctional roles of SIRT1. However, the mechanisms underlying the regulation of SIRT1 alternative splicing remain to be elucidated. Our objective is to search for new pathways that regulate of SIRT1 alternative splicing. Here we describe experiments showing that HuR and TIA1/TIAL1, two kinds of RNA-binding proteins, were involved in the regulation of alternative splicing of SIRT1 pre-mRNA under normal and stress circumstances: HuR increased SIRT1-ΔExon8 by promoting SIRT1 exon 8 exclusion, whereas TIA1/TIAL1 inhibition of the exon 8 exclusion led to a decrease in SIRT1-ΔExon8 mRNA levels. This study provides novel insight into how the alternative splicing of SIRT1 pre-mRNA is regulated, which has fundamental implications for understanding the critical and multifunctional roles of SIRT1.
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